Learn about the evolving Ebola epidemic and its various aspects including disease prevention, management and treatment, response to the epidemic, ethical considerations, and the post-Ebola global health landscape.

AH

Excellent overview with lectures by experienced experts. I really enjoyed this course.

GB

Sep 23, 2015

Filled StarFilled StarFilled StarFilled StarFilled Star

Great course on Ebola. Very engaging and intense at times. Thorough and interesting.

From the lesson

Laboratory Issues

Upon completion of this module, learners will be able to: Discuss clinical laboratory considerations for Ebola Virus Disease.Differentiate between persons under investigation and persons with confirmed EVD. Identify where and how EVD laboratory testing is performed. Recognize the safety concerns surrounding the disposal of specimens and human remains. Explore the immune response to EVD and discuss the implications for future therapeutics and vaccines.

Taught By

Dabney P. Evans, PhD, MPH

Assistant Professor

Carlos del Rio, MD

Chair

Transcript

I'm Jeannette Guarner. I'm a pathologist at the Department of Pathology and Laboratory Medicine at Emory University. I am the director of the clinical laboratory over at Emory University Hospital, Midtown. Before coming to Emory I worked at CDC for 10 years in the Pathology Department. And I got to see several cases of Ebola that were not related to this particular outbreak. So, the objectives of this particular lecture are to basically generate list of tests that need to be, performed in patients if there's a fever. And they've been going to these countries that have the outbreak right now. And to define what's causing the fever. So that would be organism specific diagnoses. We also will talk about the assessment of the patient's metabolic needs. Since one the diagnosis is made it's important for the physicians to know what's going on with the patient as far as the metabolism. Then we're going to be talking about where the tests need to be performed or can be performed. Then we'll go into describing the mechanisms that the virus used to overcome the host's defenses. And what the host uses to fight the virus. And we'll talk about recognizing some of the changes that can be seen in tissues of patients that have been infected and have died of Ebola. And then we'll talk lastly about how to dispose of specimens and human remains. So we're gonna be focused on patients that are not seen In the special communicable disease unit, here at Emory. We're gonna be focused mostly on a patient that has come from the countries that have the outbreak. And are now in a facility trying to be diagnosed of whatever they have because they have a fever. The patients that have come to Emory and have been treated here at Emory. Are patients that already knew before they even came, that they were infected with Ebola. So it's very different, the way you're going to approach these two different patients. So if you have an unknown case you're gonna basically triage the patient as far as the tests that need to be done. Depending on what the exposure has been. So we classify the patients as have high risk or low risk exposure. People that have high risk to exposure are those that have been taking care of patients. And not only taking care of patients, but in which the personal protective equipment has broken. So these patients will definitely need to be tested for Ebola. Those patients are the low risk score that will not need to be tested for Ebola, but have also come from countries like Liberia or Guinea, and have a fever. They may have other diseases and those diseases will need to be tested. But they're not Ebola, and so the physician that's looking at this patient may not need to test them for Ebola. In those cases, we may be needing to test for Malaria, we may be needing to test for Dengue Meningococcemia, typhoid, influenza. And the tests for each one of these diseases is very different. For malaria what we'll be using rapid tests, for dengue we'll be using serology. For Meningococcemia and Typhoid, we'll be using cultures. So, the material that needs to be obtained and the test that needs to be performed, will depend on what the physician thinks. It is very important because out of all the patients that have come. And you can imagine being in Atlanta there's a lot of people that the CDC has deployed to these countries. They come back and they may not be exposed to the patients because they've been doing epidemiology or triaging material. Or a variety of different things and they come back to the United States. They have a fever but what they end up having is influenza. And actually, out of all the patients that have come in that category, we've had more influenza than we've had even malaria or any of the other diseases. Now, if you have a known case, you're not only going to be testing for Ebola, and you're going to be testing for Ebola not for a diagnosis. You're going to be testing for Ebola to see what the amount of virus there is. And to see how the patient progresses in the unit, If the virus has decreased. So other things that you will be testing in these patients. You want to see what is their count of blood cells, you want to see if the patients have anemia, if their platelets are okay. You're gonna assess also what the bleeding risks are. You want to see how their electrolytes are, how there sodium is, and potassium is. And this is important because these patients come and they have a lot of diarrhea, a lot of vomiting. And so they lose all these electrolytes. And the way to bring them back is to measure those electrolytes so as to know how much of these electrolytes you will be putting in. So, it is going to be very important for people to realize that some of the test will need to be done inside the hospital where the patient is. While other tests will need to be sent to a reference laboratory. Those tests that are usually sent to a reference laboratory could be either the state health laboratory or the CDC. Then those samples will need to be wrapped in a particular way to be sent over to those locations. Well the specimens that are obtained to make sure that the patient doesn't have malaria or influenza. And to see what the metabolic state of the patient is, will likely be done in the same hospital, in house. For example, in Bellevue, or the patients that were even at Emory. Needed a lot of testing be done inside the same hospital rather than sending the test to another laboratory. The phlebotomy that needs to take place would need to take exactly all the same precautions as any of the other people that are touching the patient. Remember that the blood is one of the things that will be more infectious if this is a patient that has Ebola. So you are gonna need to have all the precautions on using or taking the specimens. And one of the things that you're gonna be doing is you're gonna be swiping the mouth. Because they're gonna get away from the patient's hospital bed, and go into another area of the hospital. So you are gonna have to clean them very carefully, put them into a container that is very sturdy. And is impermeable to fluids coming out of that container. And then you're gonna have to wipe that other container. And then take the specimen into the laboratory, where you are either going to re-pack the material for the different types of containers. So if the specimen is going to stay in the hospital once it goes into the lab it has to be opened and that would be a category b containing material. And so you can basically test it once the specimen reaches the hospital. However, if the specimen has to go to a reference laboratory, you will have to use actually two containers. You will have to put the blood in a tube, then clean it. Then put that tube Into another container that is absorbent and then into another container. And that can be shipped to either CBC or any state health department where they will basically do the testing for the Ebola. So what are the different ways we can test for Ebola? Well, immediately after the patient starts with symptoms all the tests can be negative. Some of the tests that you can do during the acute phase include antigen-capture. Or production of antibodies. Or measuring how much virus there is by looking at the nucleic material of that virus. You can also use isolation. That means growing the virus, but we don't usually do that because it's so dangerous. And the only place that does that kind of culturing technique is actually the CDC. And other laboratories that have BSL4 type facilities, which there's only four in the country. So The IgM, which is the antibody, usually takes a few days, sometimes even a week, before it becomes positive. The antigen capture can even take the same amount, or maybe even a little less, than the antibody production. So what most people are using nowadays is the measuring by polymerase chain reaction, or PCR. They're measuring the nucleic acid that's present in the blood. But the person that is infected may take a few days after symptoms have started before the PCR is positive. So sometimes with PCR a patient that is infected maybe at the very beginning of the disease, negative. But then as the virus proliferates in the patient, then become positive. This is very different from other viruses. Like for example, influenza, or right now the measles outbreak is going on. Measles and influenza tend to have production of virus very early in the disease, even before the disease is manifest. Even before the patient has a rash or the patient has any respiratory symptoms. So the patient is not only infectious before they show symptoms. But when they are tested, they are, the already have a lot of virus. In this particular case, Ebola is not infectious at the very beginning of the disease. or definitely not when they don't have symptoms. And even at the very early in the disease they may not have virus that can be detected in the blood. So that's why some people don't pass the infection in the very beginning. And that was very clearly identified in the case from Dallas. Where that patient was with his family and even had some symptoms, but none of the people that lived with him got infected. And that was likely because he didn't have enough virus in his blood to be shedding and the family around him wasn't infected. Later during the disease course the test that can be used is the formation of the antibodies. Obviously the PCR may still be positive but the antibodies is a much cheaper test that can be used. And then retrospectively, you can use other tests. You can use Immunohistochemical staining, if you take a snippet of skin. You can use PCR, or you can use virus isolation. During the acute phase, as I said the virus is gonna be seen in the blood. That's when we have a lot of virus and actually the people, the sickest people that will eventually die. Are the ones who have the highest amount of virus in their blood. But the virus can be found even after the symptoms have decreased in this disease. And so a patient that has had the infection, has had it very acutely. But then is not gonna die and is gonna be convalescent. They may continue to have virus in the blood, maybe a week later, maybe even a week and a half later. The virus is also found in other fluids like saliva, the urine, tears. We've actually seen a lot of eye disease as a part of a sequoia of patients with Ebola virus. And in their tears you can still find the virus using PCR. Other specimens that contain the virus, even long after the patient seems to have been cured are semen and vaginal secretions. So the virus, how it's shed and how long it takes for the person to get rid of can be quite long. Now there are several guidelines that have been used. There's guidelines that have been published by the CDC and by the American Society of Microbiology. That say that, if you know that the patient has Ebola, you have to do what we call point of care testing. Not only for continuing to test for Ebola, but also to measure the sodium and the potassium. And how the anemia or the blood counts are coming along. But then the menu of the tests that you can do is very very small. They also say, these guidelines, they also say that if you need to do blood cultures. Because the patient is in the hospital and gets a super infection on top of the Ebola. So that they get some sort of sepsis or something else, just because they're in the hospital. Then cultures can be done and they can be sent to the Microbiology laboratory. But once an organism is found, like say another bacteria is found, then the rest of the work for determining what kind of bacteria is present in there. Needs to be done under a hood, in containment such as what we do in Tuberculosis. As opposed to the CDC and the ASM guidelines. One of the things that is interesting is that the United Kingdom guidelines say that the specimen can go to the laboratory, even in a patient is infected. And they say that can happen because we use automated systems that use very small amounts of material. And the risk of transmission is very low, because we also dilute all the samples. However, there's as I said, the guidelines in the United States are different from the UK and we need to define exactly what we want to do. And some of the things that physicians may want to ask for on patients may not be available on point of care. Now for patients who we're trying to diagnose them for the different diseases, then definitely the samples will go to the lab. And once the patient is decided not to have Ebola but has malaria or influenza. Then there's no need to do anything, in particular, with a specimen. As far as how to discard it or anything like that. And if the patient is found later to have Ebola. Then you probably need to take those specimens and separate them from the rest. And then discard them as category A agents. So this is very important, because some of the instruments that we use in the lab have tubes that we don't even need to take the caps off. So some instruments, basically you take the tube as it comes, after it's been drawn from the patient. Put it inside the instrument, mix it so that they can do the testing. And then take the blood directly from the tube itself. And they don't need to at all, open or de-cap the tube. Other instruments, you may need to centrifuge and take the caps off. If you're gonna be doing that, there's gonna be problems. Because when you're de-capping, you create aerosols, and that's not very good. So that's why you need to use also the equipment, the masks and the face shields in the laboratory to be working with those patients. But you need to use those, regardless of if it's a patient with Ebola, or thought to have Ebola, or a person that may not have Ebola. So here's blood cultures. And the blood culture system that we nowadays use in the United States are systems that we don't need to open the bottles at all. Because they have a detector in the bottom, that allows us to see if the culture is positive or negative. So, we don't have to be taking material out and smearing it or doing any kind of seeding into plates. We're basically looking for the changes that bacteria do in the blood cultures. And then if the instrument signals that there's bacteria in there. Then we can than take the specimen in the blood culture bottle into a safety cabinet and then work from that safety cabinet. When we have to do transfusions, we will basically in patients that have Ebola, do emergency release. And then we will not do cross match in the hospital or in the blood bank. That would not be something that we would be doing.

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